Proto-proteomics: novel tools for the analysis of artificial polymer soups

The ultimate goal of the fields of origin(s) of life and artificial life is to create an artificial living system in the laboratory from the simplest possible precursors, without the aid of components derived directly from biology. There is a growing consensus that, if this ambitious goal is to be achieved, it will be through heterogeneous, multicomponent reactions that can generate a high degree of complexity. Characterising the products of such reactions presents analytical challenges that will only be overcome through the development of new tools to deal with diverse synthetic product mixtures of comparable complexity to those found in biology. The relatively recent advent of so-called ‘omics’ technologies has provided us with a suite of new analytical methodologies that could be adapted for studies into complex artificial systems. However, application of these methods, which are bespoke for biological applications, to artificial chemistries is non-trivial. In this thesis, I present novel proteomics-like approaches for analysis of complex artificial polymer soups. A model system of unconstrained, multicomponent depsipeptide elongation was used to detect the emergence of function and selection in heterogeneous synthetic polymer mixtures. This was achieved partly through the application of proteomics-like methods for screening large volumes of mass spectrometry data, without which these products could not be analysed with any reasonable throughput. Further to this, I discovered a new one-pot depsipeptide elongation and fatty acid acylation reaction driven by thermal dehydration. The fatty acid-acylated products of this reaction have the potential to form vesicles, thus providing a potential means of spontaneous compartmentalisation concomitant with the formation of diverse depsipeptide product pools. However, there were no tools available for characterising the complex mixtures of acylated and non-acylated depsipeptides produced from these reactions. I therefore developed a novel polymer sequencing software tool, adopting a more sophisticated proteomics approach for analysis of these products. While this tool has been developed using depsipeptide chemistry, I have written it with the explicit aim that, upon release to the wider artificial life community, it can be adapted for investigations into a wide variety of synthetic polymer mixtures. It is my hope that the analytical tools developed during this project will help artificial life researchers investigate heterogeneous, multicomponent polymerisation reactions that would have previously been analytically intractable